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PLoS One. 2017 Sep 26;12(9):e0184339. doi: 10.1371/journal.pone.0184339. eCollection 2017.

Two cyclic hexapeptides from Penicillium sp. FN070315 with antiangiogenic activities.

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Anticancer Agent Research Center, Korea Research Institute of Bioscience and Biotechnology, Cheongju, Republic of Korea.
Deparment of BT-Convergent Pharmaceutical Engineering, Sun Moon University, Chungnam, Republic of Korea.
Department of Biotechnology, Yonsei University, Seoul, Republic of Korea.


In the course of searching for angiogenesis inhibitors from microorganisms, two cyclic peptides, PF1171A (1) and PF1171C (2) were isolated from the soil fungus Penicillium sp. FN070315. In the present study, we investigated the antiangiogenic efficacy and associated mechanisms of 1 and 2 in vitro using human umbilical vein endothelial cells (HUVECs). Compounds 1 and 2 inhibited the proliferation of HUVECs at concentrations not exhibiting cytotoxicity. Moreover, 1 and 2 significantly suppressed vascular endothelial growth factor (VEGF)-induced migration, invasion, proliferation and tube formation of HUVECs as well as neovascularization of the chorioallantoic membrane in developing chick embryos. We also identified an association between the antiangiogenic activity of 1 and 2 and the downregulation of both the phosphorylation of VEGF receptor 2 and the expression of hypoxia inducible factor-1α at the protein level. Taken together, these results further suggest that compounds 1 and 2 will be promising angiogenesis inhibitors.

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